Generally, a disease such as cancer, acquired immunodeficiency (AIDS), cardiac disease will accompany with anorexia, weight loss, physical exhaustion, marasmus, dermatrophia, xerosis, anemia, edema, abnormal blood coagulation-fibrinolysis and this pathology is defined as cachexia. After suffering from this systemic marasmus, a patient will eventually die (Tamaguma, M. et. al., Igakuno-ayumi, 149, 371–373 (1989)). Further, if radiotherapy and/or chemotherapy is carried out for a patient with progressive or terminal cancer for whom curative operation can not be expected, it may lead to extremely lowered biological body defensive function such as immunological function due to specific malnutrition, resulting in shortening life. Therefore, there are serious problems in practical treatment of cachexia. The cause of cachexia has been so far considered to be triggered by imbalance of nutritional equilibrium resulting from lowered nutrition intake combined with increased nutrition consumption, along with affection of humoric factors mobilized from the cancer or the lesion on systemic metabolism. In the above situations, positive alimentation is carried out using total parental nutrition in order to supplement extreme nutritional or energetic deficiency and enhance immunological function in the treatment of cachexia. However, in cachexia, intake of energy will be used not for saving patient's life but for proliferation of tumor cells, so that alimentation can not be sufficient for a cachexic patient.
Recently, monokines or cytokines, such as Tumor Necrosis Factor (TNF) mobilized from macrophage, have been implicated in the pathogenesis of cachexia. TNF was found as a factor of affecting tumor cells and elucidated to be secreted by macrophages which is one of immunocytes and has a phagocytic action. Though it was originally studied as a potential anti-cancer drug because of its direct cytotoxic effect and strong anti-tumor activity, recently various kinds of action of TNF have been investigated since it was found that TNF may cause cachexia that is marasmus including weight loss of a patient with cancer, severe infectious disease, or a ringleader cytokine induced inflammation. The main actions of TNF are: (1) osteoclastic action, (2) induction of hyperlipidemia by inhibition of uptake of lipid into cell, (3) induction of production of interleukin 1 and colony stimulation factor, (4) impairment of angioendotherial cell, and (5) intervening reaction of exotoxin shock in grave infectious disease.
Though an agent for treating cachexia accompanied with cancer, acquired immunodeficient syndrome (AIDS), cardiac diseases, infectious disease, shock, burn, endotoxinemia, organ inflammation, or these diseases themselves or various kinds of inflammatory diseases including chronic rheumatoid arthritis and inflammatory gut disease are expected to be developed, in fact, there is no satisfactory agent available at present.
The present inventors found that TCF-II known as tumor cytotoxic factor has an excellent effect of preventing and treating cachexia. Accordingly, the present invention relates to an agent for preventing and/or treating cachexia comprising TCF-II as an effective ingredient.
An agent for preventing and treating cachexia caused by one of the factors selected from the group consisting of cancer, acquired immunodeficient syndrome (AIDS), cardiac diseases, infectious disease, shock, burn, endotoxinemia, organ inflammation, surgery, diabetes, collagen diseases, radiotherapy and chemotherapy is provided by the present invention.